In laboratory and clinical settings, it is often necessary to take, contain, transport and store fluid samples, such as blood or blood products, for purposes of analysis.
Liquid sample collection, handling, transport and storage has many problems associated with it including: (1) the risk of container breakage or leakage which causes loss of sample and the danger of infection; (2) sample instability during shipment and storage; (3) refusal of transport carriers to accept liquid biohazardous shipments; (4) collection of more sample than is necessary for testing, to ensure that the blood does not dry out or concentrate in the collection tube. To overcome these problems, some samples are collected on filter paper and dried prior to transport. These samples are mailable and are accepted by all common carriers. Sample stability has been demonstrated for several analytes.
Paper blood collection is currently being used by almost every newborn screening program in the U.S. [Therell 1993]. In order to test newborns for metabolic and genetic disorders, samples are obtained by heel-prick and spotted onto filter paper prior to release of the infant from the hospital or birthing center. To run an assay, a sample disk (typically a 1/8 inch or 1/4 inch circle) is punched out of the larger dried blood spot circle. This method of sample collection not only overcomes the transport and storage problems of liquid samples, but much less sample is collected. This is important because babies have a much smaller blood volume than older children or adults. It is also much easier for the phlebotomist to do a skin prick than a venipuncture on a newborn baby.
Collection of blood on paper has been used for several decades to transport blood for newborn screening. There is a standard protocol used for doing this [NCCLS, see reference 2 below]. There is also a standard paper used to collect blood samples that is universally used [Therell 1993; NCCLS, reference 2 below] in the U.S. Such standard paper is Schleicher and Schuell (Keene, N. H.) grade 903 filter paper. In 1976, Mitchell [see reference 3] described an assay for thyroxine in dried blood spots to detect hypothyroid infants. Travis et al. (1979) evaluated two commercial methods for measuring thyroid hormones in dried blood spots. These commercial methods included reference standards (calibrators) and controls dried on paper. Hearn and Hannon (1982) described an interlaboratory survey in which dried filter spots, made by the Centers for Disease Control (CDC), were assayed by many laboratories. In this article, the authors describe a method for dispensing the blood onto the paper. This procedure entails dispensing blood (100 .mu.L) within 12-mm circles stamped (or printed) onto the filter paper. During the dispensing process, the papers were held in a flat horizontal position by doublestick tape to wooden rails. This was done in order to lift the paper off of the surface and to keep the paper from curling-up (bending) during the drying process. The blood spots papers were dried overnight attached to the wooden rails. Similar surveys were later reported by Spierto et al. [see reference 6] and Slazyak et al. (1988). In the latter, the effects of using printed versus unprinted paper on absorbency is discussed. There may be a loss of absorbency due to the compression of the printed ring during the printing process. Spencer et al. (1993) reported the use of filter paper spot blood collection in screening adult samples for Down Syndrome carriers by measuring chorionic gonadotropin (hCG). They stated that hCG is unstable when stored in liquid blood after several days, and report that filter paper dried blood collection is the method of choice. O'Broin (1993) showed that blood viscosity differences can result in blood volume differences in paper spots due to "spreadability" of the blood during dispensing.
For purposes of convenience, efficiency and the desire to have multiple samples to assure repeatability, it is often the case that a number of sample spot zones are placed in close proximity to one another on a single absorbent paper. One of the difficulties in the use of paper spot sampling is avoiding cross contamination of adjacent sample spot zones. Accordingly, it is desirable to be able to produce a sampling paper that resists sample spreading by capillary action. It is also desirable to produce paper-spotted controls and calibrators, for use with assay techniques using paper spot samplings, which can be prepared while resisting spreading and cross-contamination.